WikiPathways: building research communities on biological pathways

Kelder, Thomas; Iersel, Martijn P. van; Hanspers, Kristina; Kutmon, Martina; Conklin, Bruce R.; Evelo, Chris T.; Pico, Alexander R.

doi:10.1093/nar/gkr1074

Cited by 475 publications

(384 citation statements)

References 23 publications

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“…The genes were also analyzed for presence of Sox9-binding site in their promoter region using the GeneQuest program from Lasergene package from DNASTAR. Genes from this subgroup were ordered into known pathways and analyzed using Pathvisio software (18). These data show a high prevalence of potential SOX9 target genes in cancer relevant pathways including the CXCR4, focal adhesion, retinoic acid, and WNT pathways.…”

Section: Pathway Analysis and Expression Of Sox9 Target Genesmentioning

confidence: 99%

Hypoxia-Independent Gene Expression Mediated by SOX9 Promotes Aggressive Pancreatic Tumor Biology

Čamaj

Jäckel

Krebs

et al. 2014

Molecular Cancer Research

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Pancreatic cancer aggressiveness is characterized by its high capacity for local invasion, ability to promote angiogenesis, and potential to metastasize. Hypoxia is known to represent a crucial step in the development of aggressive malignant features of many human cancers. However, micrometastatic tumors are not typically subjected to hypoxic events during early stages of dissemination; therefore, it is unclear how these tumors are able to maintain their aggressive phenotype. Thus, the identification of regulators of hypoxia-related genes in aggressive/ metastatic tumors represents a fundamental step for the design of future therapies to treat pancreatic cancer. To this end, transcriptomic profiles were compared between the nonmetastatic pancreatic cancer cell line FG (LMET) and its angiogenic/metastatic derivate L3.6pl (HMET) under normoxic or hypoxic conditions. Cluster analysis revealed a number of transcripts that were induced by hypoxia in nonmetastatic cancer cells. Strikingly, this cluster was determined to be constitutively activated under normoxia in the metastatic cancer cells and could not be further induced by hypoxia. A subset of these transcripts were regulated by the transcription factor SOX9 in the aggressivemetastatic cells, but driven by hypoxia-inducible factor-1a (HIF-1a) in the parental nonmetastatic cell line. Moreover, these transcripts were enriched in cancer-related networks including: WNT, CXCR4, retinoic acid, and (FAK) focal adhesion kinase, gene PTK2 signaling pathways. In functional assays, inhibition of SOX9 expression in HMET cells led to increased apoptosis and reduced migration in vitro and a significant reduction in primary tumor growth, angiogenesis, and metastasis following orthotopic tumor cell injection. At the molecular level, the control of SOX9 expression was associated with changes in the methylation status of the SOX9 promoter. Finally, SOX9 upregulation was verified in a series of tumor specimens of patients with pancreatic carcinoma.

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Section: Pathway Analysis and Expression Of Sox9 Target Genesmentioning

confidence: 99%

Hypoxia-Independent Gene Expression Mediated by SOX9 Promotes Aggressive Pancreatic Tumor Biology

Čamaj

Jäckel

Krebs

et al. 2014

Molecular Cancer Research

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“…We applied gene list enrichment analysis using the BioCarta, KEGG (Kyoto Encyclopedia of Genes and Genomes [KEGG]), 17 WikiPathways, 18 ChIP-seq/chip enrichment analysis (ChEA), 19 kinase enrichment analysis (KEA), 20 protein interaction hubs, Mouse Genome Informatics-Mammalian Phenotype, 21 and Human Gene Atlas (cell types expression) 22 gene set libraries implemented within our software tools Lists2Networks 23 and Expression2Kinases 24 (Supplemental Tables 4-7). These tools use the Fisher exact test to compute P values for probability for overlap between two independent sets of genes.…”

Section: Pathway Analysis Of Genes Altered In Tg26 Kidneys and Predicmentioning

confidence: 99%

“…Cr, creatinine; WT, wild-type. pathways are based on WikiPathways 18 ( Figure 4A and Supplemental Table 4). Hence, trichostatin A is an anti-inflammatory drug that reduces inflammation in the kidneys of HIVAN mice, where it is probably acting through the IL and NFkB pathways.…”

Section: Pathway Analysis Of Genes Altered In Tg26 Kidneys and Predicmentioning

confidence: 99%

Renoprotective Effect of Combined Inhibition of Angiotensin-Converting Enzyme and Histone Deacetylase

Zhong

Chen

Liu

et al. 2013

Journal of the American Society of Nephrology

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The Connectivity Map database contains microarray signatures of gene expression derived from approximately 6000 experiments that examined the effects of approximately 1300 single drugs on several human cancer cell lines. We used these data to prioritize pairs of drugs expected to reverse the changes in gene expression observed in the kidneys of a mouse model of HIV-associated nephropathy (Tg26 mice). We predicted that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a histone deacetylase inhibitor would maximally reverse the disease-associated expression of genes in the kidneys of these mice. Testing the combination of these inhibitors in Tg26 mice revealed an additive renoprotective effect, as suggested by reduction of proteinuria, improvement of renal function, and attenuation of kidney injury. Furthermore, we observed the predicted treatment-associated changes in the expression of selected genes and pathway components. In summary, these data suggest that the combination of an ACE inhibitor and a histone deacetylase inhibitor could have therapeutic potential for various kidney diseases. In addition, this study provides proof-of-concept that drug-induced expression signatures have potential use in predicting the effects of combination drug therapy.

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“…All metabolic and non-metabolic pathways were downloaded from the open WikiPathways (Pico et al, 2008;Kelder et al, 2012) database, and conducted Wikipathways cluster analysis (Zhang et al, 2005;Duncan et al, 2010) to the DEGs by Gene Set Analysis Toolkit V2 platform. The count number larger than 2 and p-value less than 0.00001 were chosen as cut-off criterion.…”

Section: Biological Pathway Enrichment Analysismentioning

confidence: 99%

Identifying Differentially Expressed Genes and Small Molecule Drugs for Prostate Cancer by a Bioinformatics Strategy

Ye²,

Lu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Purpose: Prostate cancer caused by the abnormal disorderly growth of prostatic acinar cells is the most prevalent cancer of men in western countries. We aimed to screen out differentially expressed genes (DEGs) and explore small molecule drugs for prostate cancer. Materials and Methods: The GSE3824 gene expression profile of prostate cancer was downloaded from Gene Expression Omnibus database which including 21 normal samples and 18 prostate cancer cells. The DEGs were identified by Limma package in R language and gene ontology and pathway enrichment analyses were performed. In addition, potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify potential small molecule drugs. Results: A total of 6,588 genes were filtered as DEGs between normal and prostate cancer samples. Examples such as ITGB6, ITGB3, ITGAV and ITGA2 may induce prostate cancer through actions on the focal adhesion pathway. Furthermore, the transcription factor, SP1, and its target genes ARHGAP26 and USF1 were identified. The most significant microRNA, MIR-506, was screened and found to regulate genes including ITGB1 and ITGB3. Additionally, small molecules MS-275, 8-azaguanine and pyrvinium were discovered to have the potential to repair the disordered metabolic pathways, abd furthermore to remedy prostate cancer. Conclusions: The results of our analysis bear on the mechanism of prostate cancer and allow screening for small molecular drugs for this cancer. The findings have the potential for future use in the clinic for treatment of prostate cancer.

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WikiPathways: building research communities on biological pathways

Cited by 475 publications

References 23 publications

Hypoxia-Independent Gene Expression Mediated by SOX9 Promotes Aggressive Pancreatic Tumor Biology

Hypoxia-Independent Gene Expression Mediated by SOX9 Promotes Aggressive Pancreatic Tumor Biology

Renoprotective Effect of Combined Inhibition of Angiotensin-Converting Enzyme and Histone Deacetylase

Identifying Differentially Expressed Genes and Small Molecule Drugs for Prostate Cancer by a Bioinformatics Strategy

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